法尼甾体X受体
CYP8B1
胆酸
胆汁酸
G蛋白偶联胆汁酸受体
肝肠循环
孕烷X受体
胆固醇7α羟化酶
鹅去氧胆酸
胆酸
肝受体同系物-1
核受体
CYP27A1
胆盐出口泵
内科学
小异二聚体伴侣
脱氧胆酸
生物
生物化学
内分泌学
转录因子
运输机
医学
基因
作者
Tsutomu Matsubara,Fei Li,Frank J. Gonzalez
标识
DOI:10.1016/j.mce.2012.05.004
摘要
Enterohepatic circulation serves to capture bile acids and other steroid metabolites produced in the liver and secreted to the intestine, for reabsorption back into the circulation and reuptake to the liver. This process is under tight regulation by nuclear receptor signaling. Bile acids, produced from cholesterol, can alter gene expression in the liver and small intestine via activating the nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR is known to be a major bile acid-responsive ligand-activated transcription factor and a crucial control element for maintaining bile acid homeostasis. FXR has a high affinity for several major endogenous bile acids, notably cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to excess bile acids, FXR is a bridge between the liver and small intestine to control bile acid levels and regulate bile acid synthesis and enterohepatic flow. FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism.
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